CLIC4 is a highly conserved, multifunctional member of the chloride intracellular channel family of proteins. The protein is largely cytoplasmic but translocates to the nucleus upon a variety of stimuli including TGF-beta, TNF-alpha and etoposide. Nuclear resident CLIC4 causes growth arrest, terminal differentiation and apoptosis. Recently, it was discovered that TGF-beta causes CLIC4 to associate with Schnurri-2 and together they translocate to the nucleus and dissociate thereafter. The nuclear function of CLIC4 was further illuminated by the discovery that CLIC4 enhances TGF-beta signaling by associating with phospho-Smad2 and 3 and preventing their dephosphorylation. Enhanced TGF-beta dependent gene expression and growth inhibition are downstream consequences of this activity of CLIC4. In this article, we speculate on other consequences of the CLIC4 relation to TGF-beta signaling and the potential for CLIC4 to participate in other cellular functions related to normal homeostasis and disease.

中文翻译：

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CLIC4 和 Schnurri-2：TGFβ 信号传导中的动态二重奏，对细胞稳态和疾病具有更广泛的影响

CLIC4 是氯离子细胞内通道蛋白家族的一个高度保守的多功能成员。该蛋白质主要在细胞质中，但在各种刺激下转移到细胞核，包括 TGF-β、TNF-α 和依托泊苷。核驻留 CLIC4 导致生长停滞、终末分化和细胞凋亡。最近，发现 TGF-β 导致 CLIC4 与 Schnurri-2 结合，它们一起转移到细胞核并随后解离。CLIC4 的核功能通过发现 CLIC4 通过与磷酸 Smad2 和 3 结合并防止它们去磷酸化来增强 TGF-β 信号传导而得到进一步阐明。增强的 TGF-β 依赖性基因表达和生长抑制是 CLIC4 活性的下游结果。在本文中，